Chemical proteomics unveils that seventy flavors pearl pill ameliorates ischemic stroke by regulating oxidative phosphorylation.

Ischemic stroke has high mortality and morbidity rates and is the second leading cause of death in the world, but there is no definitive medicine. Seventy Flavors Pearl Pill (SFPP) is a classic formula in Tibetan Medicine. Clinical practice has shown the attenuation effect of SFPP on blood pressure disorders, strokes and their sequelae and other neurological symptoms, but its mechanism remains to be elucidated. In this study, we established three animal models in vivo and three cell models to evaluate the anti-hypoxia, anti-ischemia, and reperfusion injury prevention effects of SFPP. Quantitative proteomics revealed that oxidative phosphorylation (OXPHOS) is essential for SFPP's efficacy. Then, cysteine-activity based protein profiling technology, which reflects redox stress at the proteome level, was employed to illustrate that SFPP brought functional differences of critical proteins in OXPHOS. In addition, quantitative metabolomics revealed that SFPP affects whole energy metabolism with OXPHOS as the core. Finally, we performed a compositional identification of SFPP to initially explore the components of potential interventions in OXPHOS. These results provide new perspectives and tools to explore the mechanism of herbal medicine. The study suggests that OXPHOS could be a potential target for further research and intervention of ischemic stroke treatment.

Proteomics and Metabolomics Unveil Codonopsis pilosula (Franch.) Nannf. Ameliorates Gastric Precancerous Lesions via Regulating Energy Metabolism.

Objective: This study aimed to systematically evaluate the efficacy of Codonopsis pilosula (Franch.) Nannf. (Codonopsis Radix, CR) and reveal the mechanism of its effects on suppressing Gastric Precancerous Lesions. Methods: First, we established the GPL rat model which was induced by N-methyl-N'-nitro-N-nitrosoguanidine, a disordered diet, and 40% ethanol. The CR's anti-Gastric Precancerous Lesions effect was comprehensively evaluated by body weight, pathological section, and serum biochemical indexes. Then, quantitative proteomics and metabolomics were conducted to unveil the disturbed protein-network and pharmacodynamic mechanism. Furthermore, serum pharmacology was employed to confirm that CR's anti-gastritis and anti-cancer phenotype in cell models. Results: In animal models, CR had been shown to control inflammation and ameliorate Gastric Precancerous Lesions. Considering the combination of proteomics and metabolomics, we found that CR could significantly reverse the biological pathways related to energy metabolism which were disturbed by the Gastric Precancerous Lesions model. Furthermore, the results of serum pharmacology indicated that the Codonopsis Radix containing serum could ameliorate gastritis injury and selectively inhibit the proliferation of gastric cancer cells rather than normal cells, which was closely related to ATP production in the above mentioned cells. Conclusion: In summary, CR exerted anti-Gastric Precancerous Lesions effects by ameliorating gastritis injury and selectively inhibiting the proliferation of gastric cancer cells rather than normal cells. Proteomics and metabolomics unveiled that its efficacy was closely related to its regulation of the energy-metabolism pathway. This research not only provided new ideas for exploring the mechanism of complex systems such as Chinese herbals but also benefited the treatment strategy of Gastric Precancerous Lesions via regulating energy metabolism.

Quantitative Proteomics Revealed the Pharmacodynamic Network of Bugu Shengsui Decoction Promoting Osteoblast Proliferation.

Background and Objective: With high morbidity and disability, osteoporosis is a worldwide bone metabolism disease, regulated by complex pathological processes. Insufficient osteogenesis is greatly essential to osteoporosis. Traditional Chinese Medicine, a complex natural herbal medicine system, has increasingly attracted attention all over the world. Bugu Shengsui Decoction, a compound formula for osteoporosis, has significant clinical effects in the treatment of osteoporosis. Yet the detailed mechanisms are unclear. Thus, we investigated the effects and mechanism of Bugu Shengsui Decoction on osteoporotic rats and osteoblasts in vitro. Methods: In this study, we evaluated the effect of Bugu Shengsui Decoction in an animal model of orchiectomy. Multi-pharmacology indexes revealed that Bugu Shengsui Decoction obviously improved bone metabolism, bone mineral density, bone morphology, and biomechanics in the castrated rats. Then, serum pharmacology was employed to unveil that Bugu Shengsui Decoction promoted the proliferation and differentiation of osteoblasts. Moreover, quantitative proteomics combined with RNA interference assay was used to analyze and verify the pathway and key targets in pro-proliferation of MC3T3-E1 cells. Results: Bugu Shengsui Decoction obviously improved the worse parameters of bone metabolism, bone mineral density, bone morphology, and biomechanics in a castrated rat model. In vitro, Bugu Shengsui Decoction exerted proliferation- and differentiation-promoting effects of osteoblasts induced by serum starvation. Moreover, quantitative proteomics analysis combined with RNA interfere assay illustrated that Bugu Shengsui Decoction promoted osteogenesis via the PI3K-AKT pathway. Conclusion: Summarily, our discoveries certify that Bugu Shengsui Decoction is an effective treatment for osteoporosis via PI3K-AKT. This study is not only a beneficial attempt to explore the detailed mechanism of Traditional Chinese formula but also will provide inspiration for the treatment strategy of osteoporosis.

A nano silicon adjuvant enhances inactivated transmissible gastroenteritis vaccine through activation the Toll-like receptors and promotes humoral and cellular immune responses.

Inactivated transmissible gastroenteritis virus (TGEV) vaccines are widely used in swine herds in China. These are limited, however, by the need to elicit both humoral and cellular immunity, as well as the efficiency of adjuvants. In this study, a 70-nm nano silicon particle was applied with inactivated TGEV vaccine in mice, and its immune-enhancing effects and mechanism of action investigated. We found that nano silicon applied with inactivated TGEV vaccine induced high antibody titers, increase IL-6, TNF-α and IFN-γ expression, and stimulate CD3+ T cell proliferation with a high CD4+/CD8+ T lymphocyte ratio. Nano silicon could quickly activate innate and adaptive immunity by stimulating Toll-like receptor signaling pathways, indicating that the nano silicon adjuvant enhanced long-term humoral and early cellular immune responses when combined with inactivated TGEV vaccine. Nano silicon could be considered for use as an antigen- carrier and adjuvant for veterinary vaccines.

Relationship between cystatin C and metabolic syndrome among Chinese premenopausal and postmenopausal women without recognized chronic kidney disease.

OBJECTIVE: Although studies have shown that elevated cystatin C (Cys-C) levels are associated with the risk of metabolic syndrome (MetS) in the general population, few studies have examined the relationship between serum Cys-C levels and MetS, stratified by menopause status, among women in China. Therefore, we conducted this study to assess the relationship between Cys-C levels and MetS in Chinese premenopausal and postmenopausal women. METHODS: We performed a cross-sectional analysis of the baseline data of 1,428 Chinese community-dwelling women who participated in the annual health checkup. MetS was defined by the updated National Cholesterol Education Program/Adult Treatment Panel III criteria. Binary logistic regression analysis was performed to estimate the association between Cys-C levels and MetS. One-way analysis of variance, followed by posttest for linear trends, was performed to evaluate the relationships between Cys-C levels and the number of MetS components. Ordinal regression analysis was used to determine whether menopause status and MetS components contribute to elevated levels of Cys-C. RESULTS: The mean level of Cys-C was significantly higher in women with MetS than in those without MetS among both premenopausal and postmenopausal women, showing a progressive increase (P for trend < 0.001) in parallel with the progressive increment in the number of MetS components in all women. Higher Cys-C levels were found to be associated with the presence of MetS after adjusting for age, body mass index, and estimated glomerular filtration rate in all women. The higher odds ratio changed little, even after further adjustment for serum blood nitrogen, total cholesterol, low-density lipoprotein cholesterol, drinking status, and smoking status. Elevated Cys-C level was significantly associated with postmenopause status (P = 0.007), increased waist circumference (P = 0.006), and elevated blood pressure (P = 0.025). CONCLUSIONS: Higher serum Cys-C levels are positively and independently associated with the presence of MetS in Chinese premenopausal and postmenopausal women. Elevated Cys-C levels are significantly associated with postmenopause status.

[Relationship between normal serum uric acid levels and nonalcoholic fatty liver disease in postmenopausal women].

OBJECTIVE: To analyze the relationship between normal serum uric acid (SUA) levels and nonalcoholic fatty liver disease (NAFLD) among postmenopausal women, and determine the possible risk factors of NAFLD in this patient population. METHODS: Chinese postmenopausal women who participated in the annual health check-up program from March 2009 to February 2010 were retrospectively assessed to identify individuals with SUA within normal range for study inclusion. For the total 1425 study participants, the recorded data of anthropometric parameters, metabolic factors, and serum biochemical parameters were collected. Results from abdominal ultrasonography examination were used to group participants according to presence of fatty liver. Women with fatty liver were divided into NAFLD and non-NAFLD groups. Further sub-grouping was performed according to SUA quartiles, as follows: Q1 group: less than 226.1 mumol/L); Q2 group: 226.1 mumol/L less than or equal to SUA less than 267.8 mumol/L; Q3 group: 267.8 mumol/Lless than or equal to SUA less than 303.5 mumol/L); Q4 group: 303.5 mumol/Lless than or equal toSUAless than or equal to357.0 mumol/L. The independent-sample t-test was used to compare normally distributed variables between groups, and the Mann-Whitney U test was used to analyze variables with skewed distribution. Categorical variables were examined by the R * C x2 test. Binary logistic analysis was used to determine the risk factors for fatty liver and to adjust for possible confounders. The multiple non-parameter independent-sample test (Kruskal-Wallis test) was used to compare the differences of SUA levels among NAFLD groups with different disease severity. RESULTS: The prevalence of NAFLD among Chinese postmenopausal women with normal SUA was 32.8%, with NAFLD prevalences of 20.4% (70/343) in women with Q1 SUA, 26.3% (104/395) with Q2 SUA, 35.2% (128/364) with Q3 SUA, and 51.4% (166/323) with Q4 SUA. The prevalence of fatty liver showed a significant increasing trend according to the SUA quartile (x2 = 76.470, P-trend less than 0.01). Women in the SUA Q3 and Q4 groups had significantly higher risk of fatty liver presence than women in the Q1 group (P less than 0.01 for both, with or without adjustment of confounders). Disease severity did not appear to be related to disease severity, as the SUA levels in women with mild, moderate or severe fatty liver were not significantly different (286.8+/-48.2 mumol/L vs. 277.9+/-53.0 mumol/L vs. 281.4+/-48.2 mumol/L, respectively; x2 = 3.025, P more than 0.05). CONCLUSION: SUA levels were independently correlated with NAFLD in Chinese postmenopausal women. SUA levels in the higher quartiles of the normal range may be an independent risk factor of NAFLD.

Utility of obesity indices in screening Chinese postmenopausal women for metabolic syndrome.

OBJECTIVE: Although a variety of indices have been used to assess obesity, which is closely associated with the development of metabolic syndrome (MetS), the best indicator of the effects of fat accumulation on Chinese postmenopausal women is still uncertain. Thus, the objectives of this study were to analyze the potential of different obesity indices and to explore which index is best for predicting MetS in Chinese postmenopausal women. METHODS: A cross-sectional analysis of the baseline data of 1,234 Chinese postmenopausal women (aged 42-79 y) who participated in the annual health checkup was performed. The obesity indices of all participants, including body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), percent body fat (PBF), and fat mass index (FMI), were measured or calculated. The updated National Cholesterol Education Program/Adult Treatment Panel III criteria were used to assess MetS risk factors. Spearman and partial correlations were used to assess correlations between obesity indices and MetS components. The area under the curve of the receiver operating characteristic (ROC) curve was used to determine the optimal cutoff values of all indicators of MetS development. The values of BMI, WC, WHR, WHtR, PBF, and FMI that resulted in the maximization of the Youden index (sensitivity + specificity - 1) were defined as optimal. RESULTS: Among the participants, 38.8% (n = 479) were identified as having two or more nonadipose MetS risk components (excluding a positive WC component). These women had higher obesity indices than women with fewer metabolic risk factors. All indices were significantly associated with all MetS components even after controlling for age and C-reactive protein. A BMI of 24.0 kg/m, a WHR of 0.85, a WC of 79.9 cm, a WHtR of 0.49, a PBF of 29.9%, and an FMI of 7.2 kg/m were the optimal cutoff values for predicting at least two other MetS components according to ROC curve analysis. However, among the indicators of central obesity, WHR and WHtR showed the greatest area under the ROC curve. CONCLUSIONS: WHR and WHtR are the best indicators of MetS development. A WHR of 0.85 or higher and a WHtR of 0.49 or higher should be incorporated into the identification of MetS risk in Chinese postmenopausal women.

A finite-element approach for Young's modulus reconstruction.

Modulus imaging has great potential in soft-tissue characterization since it reveals intrinsic mechanical properties. A novel Young's modulus reconstruction algorithm that is based on finite-element analysis is reported here. This new method overcomes some limitations in other Young's modulus reconstruction methods. Specifically, it relaxes the force boundary condition requirements so that only the force distribution at the compression surface is necessary, thus making the new method more practical. The validity of the new method is demonstrated and the performance of the algorithm with noise in the input data is tested using numerical simulations. Details of how to apply this method under clinical conditions is also discussed.

In vivo real-time freehand palpation imaging.

Previous experience with laboratory fixtures and off-line processing of elasticity data showed that problems occurring in data acquisition often resulted in poor elasticity image quality. A system for real-time estimation and display of tissue elastic properties using a clinical ultrasonic imaging system has been developed. A brief description of that system and the initial clinical tests of that system are reported. Experience with real-time freehand elasticity imaging shows that images with high contrast-to-noise ratios are consistently obtained. Images of breast lesions were acquired with freehand palpation using standard linear-array ultrasound (US) transducers. Results in volunteer patients show that high-quality elasticity images are easily obtained from in vivo breast studies. The key element to successful scanning is real-time visual feedback of B-mode and strain images that guide the patient positioning and compression direction. Results show that individual images of axial strain in tissues can be quite misleading, and that a "movie loop" of side-by-side B-mode and strain images provides significantly more information. Our preliminary data suggest that the strain image sequences for various breast pathologies are unique. For example, strain images of fibroadenomas lose contrast with increasing precompression, but those of invasive ductal carcinoma have high negative contrast (dark relative to "normal" tissue) for a wide range of precompression. In addition, a comparison of the lesion area measured in B-mode vs. strain images, for a representative image from the sequence, appears to be a sensitive criterion for separating invasive ductal carcinoma from cyst and fibroadenoma.

A modified block matching method for real-time freehand strain imaging.

This manuscript reports a technical innovation that has been developed for real-time, freehand strain imaging. This work is based on a well-known block-matching algorithm with two significant modifications. First, since displacements are estimated row-by-row, displacement estimates from the previous row are used to predict the displacement estimates in the current row, thereby drastically reducing the search-region size and increasing computational efficiency. Second, a displacement error detection and correction method is developed to overcome the local tracking errors that may be more severe with freehand scanning and thereby improve the robustness of the algorithm. This algorithm has been implemented on a clinical ultrasound imaging system, and with real-time imaging feedback, long sequences of high quality strain images are observed using freehand compression. Displacement estimation errors with this method are experimentally measured and compared with results from simulation. We report only a specific implementation, with no comparison to other displacement estimators in the literature and no optimization of this specific technique. Images of tissue-mimicking phantoms with small spherical targets are used to test the ability to detect small lesions using the strain imaging technique. In vivo strain images of breast and thyroid are also shown.